多卢特格拉维尔和神经精神疾病不良事件的风险:药物遗传学研究
Julien De Greef1,2, Jean Cyr Yombi2, Anne Vincent2
1Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
The Journal of infectious diseases
|March 4, 2025
概括
药物基因的遗传变异可以在杜洛特格拉维尔治疗期间影响神经精神病学不良事件 (NPAE). 一种特定的NR1I2基因变异与由于NPAE而停止服用杜洛特格拉维尔的风险较低有关.
科学领域:
- 药物基因组学 药物基因组学
- 神经精神病学是一种神经精神病学.
- 药物新陈代谢 药物新陈代谢
背景情况:
- 多卢特格拉维尔是一种有效的抗逆转录病毒药物.
- 神经精神病学不良事件 (NPAE) 是杜洛特格拉维尔治疗的潜在副作用.
- 个人的遗传构成可能会影响对NPAE的易感性.
研究的目的:
- 调查药物基因中的遗传多态化与用多卢特格拉维尔治疗的患者中NPAE的发生之间的关联.
- 为了确定基因标记,可以预测杜洛特格拉维尔诱导的NPAE的风险.
主要方法:
- 采用了一种病例控制研究设计.
- 36名因NPAE (病例) 暂停服用杜洛特格拉维尔的患者与98名耐受杜洛特格拉维尔的患者 (对照) 进行了比较.
- 下一代测序小组测试被用于确定多态性在dolutegravir相关的药物基因.
主要成果:
- NR1I2 c.-22-7659C>T多态性独立地与由于NPAE (OR 0.36;95% CI, .15-.88为T变异型等位基因携带) 而导致杜洛特格拉维尔中止的风险降低有关.
- 在耐受多卢特格拉维尔的患者中,携带NR1I2c.-22-7659C>T的T变异异基因与降低焦虑评分有关.
结论:
- 遗传变异,特别是在NR1I2基因中,可能在与杜洛特格拉维尔相关的NPAE的发展中发挥作用.
- NR1I2 c.-22-7659C>T多态性可以作为杜洛特格拉维尔耐受性的预测生物标志物,以预测其对神经精神疾病的影响.
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